For the production of the above cysteine derivative (III), there is already known the technology by which an R.sup.3 -S group is introduced into a compound whose amino and carboxyl groups have been protected, for example the process which comprises transforming the hydroxyl group of a serine derivative Into a leaving group and then conducting a substitution reaction [Tetrahedron Letters, 28, 6069 (1987), ibid, 34, 6607 (1993), and EP 604185A1].
However, this technology involves transformation of the hydroxyl group of a serine derivative into a sulfonyloxy group and a subsequent substitution reaction with the sodium salt of a thiol in anhydrous N,N-dimethylformamide. None of the available literature refer to the impurity by-produced in the reaction, but our investigation revealed that, in this reaction, there is a problem that the sodium salt of thiol or its derivatives, which acts as a base, causes abstraction of the carbonyl .alpha.-hydrogen and subsequent E2 elimination in competition with the objective substitution reaction to give the dehydroalanine derivative of the following general formula (IV) [hereinafter referred to as dehydroalanine derivative (IV)], with the result that the yield of the objective compound is decreased.
We also found that, when the objective cysteine derivative (III) is an optically active compound, a Michael addition of the thiol to the dehydroalanine derivative (IV) so produced may further cause the objective cysteine derivative (III) to reduce the optical purity thereof. ##STR5##
In the above reaction scheme, R.sup.1, R.sup.2, and R.sup.3 are as defined above; X represents a leaving group.
Furthermore, as a production method of the thiol salt for use in the reaction, a method using sodium hydride or potassium hydride under anhydrous conditions have been used but, from the standpoint of handling, the method cannot be said to be suitable for industrial application.
Under the circumstances, the present invention has for its object to provide a process for producing a cysteine derivative, which is economical, high in production efficiency even in a commercial operation, and especially insuring a high optical purity of the objective compound.